The semisynthesis of morphine-derived antagonists, such as naloxone, see compound 5 below, and naltrexone see compound 6 below, and other medicinally significant compounds, from opium-derived natural products traditionally involves standard procedures for demethylation followed by subsequent procedures such as oxidative procedures for the introduction of a C-14 hydroxyl group.

Most commercial procedures for the production of C-14 hydroxylated species take advantage of Δ7-8 unsaturated species, however compounds containing α, β-unsaturated ketones have recently been identified as potential genotoxins because of their Michael acceptor character, and therefore routes to the oxygenated derivatives must avoid these intermediates.
Therefore any method that avoids these standard procedures may hold immense commercial potential for the production of morphine-derived antagonists, such as naloxone 5, naltrexone 6, and other medicinally significant compounds.
The development of a mild catalytic protocol for N-demethylation of ring-C saturated morphinans would simplify strategies toward C-14 oxygenated derivatives via potential use of an intramolecular process by tethered functionalisation anchored at the nitrogen atom.
N-Demethylation of morphine-type alkaloids has been extensively studied. The standard procedures for N-demethylation of substrates including morphinan derived compounds include the use of cyanogen bromide (the von Braun reaction)1, the reaction of a tertiary amine with chloroformates followed by hydrolysis2, as well as a photochemical demethylation procedure3. Other methods that have been used to effect demethylation include amongst others, Polonovski-type reactions4. Precedent for a Pd-catalyzed oxidative demethylation procedure using stoichiometric amounts of Pd/C, appears in a single report by Chaudhuri5.
Chaudhuri's method describes the use of Pd/C (1 g/1 g substrate) in MeOH at room temperature to dealkylate tertiary amines. On occasion he notes that small amounts of N-formyl species were isolated. This was an undesired side reaction for his methodology. Application of the conditions described in this paper to hydrocodone results in no N-demethylation. The only product recovered was N-formyl hydrocodone. Thus, there remained a need for a truly practical method for the production of demethylated morphine derivatives.